Intellia Therapeutics, Inc. Q4 FY2024 Earnings Call

Good morning, and welcome to Intellia Therapeutics' Fourth Quarter and Full-Year 2024 Financial Results Conference Call. My name is Drew, and I will be your conference operator today. Following formal remarks, we will open the call for a question-and-answer session. This conference is being recorded at the Company's request and will be available on the Company's website after the call ends. As a reminder, all participants are currently in a listen-only mode. I will now turn the conference over to Brittany Chaves, Manager of Investor Relations at Intellia. Please proceed.

Thank you, operator, and good morning, everyone. Welcome to Intellia Therapeutics' fourth quarter and full-year 2024 earnings call. Earlier this morning, Intellia issued a press release outlining the Company's progress this quarter, as well as topics for discussion on today's call. This release can be found on the Investors and Media section of Intellia's website at intelliatx.com. This call is being broadcast live and a replay will be archived on the Company's website. At this time, I'd like to take a minute to remind listeners that during this call, Intellia management may make certain forward-looking statements and ask that you refer to our SEC filings available at sec.gov for discussion of potential risks and uncertainties. All information presented on this call is current as of today, and Intellia undertakes no duty to update this information unless required by law. Joining me from Intellia are John Leonard, Chief Executive Officer; David Lebwohl, Chief Medical Officer; Ed Dulac, Chief Financial Officer; and Birgit Schultes, our Chief Scientific Officer who will join for Q&A. John will begin with recent business highlights, David will then provide updates on our clinical pipeline progress, and Ed will review our financials before we open the call for questions. With that, I will now turn the call over to John, our Chief Executive Officer.

Thank you, Brittany. Good morning, everyone, and thank you all for joining us today. We are off to a strong start in 2025 with renewed focus on our operational execution. The growing support and interest from investigators and patients are making remarkable headway with enrollment across our late-stage studies. We see significant promise with NTLA-2002 for the treatment of hereditary angioedema where we expect complete enrollment in our Phase III study HAELO in the second half of 2025. We are similarly encouraged by the pace of enrollment with our Phase III studies for transthyretin amyloidosis and expect enrollment in MAGNITUDE, our cardiomyopathy study to exceed 550 total patients by year-end. Both HAE and TTR represent substantial market opportunities. We have doubled down on our efforts to ready the company for the rapidly approaching commercial phase. In November, we presented positive extended follow-up data from patients in the ongoing Phase I trial of nex-z, previously known as NTLA-2001 in patients with transthyretin or ATTR amyloidosis. The Phase I data offered compelling evidence that deep and persistently low levels of TTR reduction achieved with nex-z may favorably impact disease progression for people living with ATTR amyloidosis. David will review these results in greater detail. We are actively screening patients with ATTR amyloidosis with polyneuropathy in our Phase III MAGNITUDE-2 study and are on track to dose the first patient in the coming weeks. As you may recall, this pivotal trial is an efficient study with expected enrollment of 50 patients. We plan to measure mNIS+7 at 18 months, and serum TTR levels as key endpoints in the study. We expect enrollment to be completed in 2026, enabling their second BLA filing by 2028. Last month, we announced the first patient had been dosed with NTLA-2002 in HAELO, our Phase III study in HAE. Enthusiasm for NTLA-2002 from patients and our investigators is high, and we believe this Phase III study will enroll rapidly, enabling us to submit a BLA filing in 2026. At the beginning of this year, we conducted a pipeline prioritization to focus our resources and efforts on these late-stage and high-value programs NTLA-2002 and nex-z. We discontinued our work on NTLA-3001 in favor of a second-generation approach, and we'll now look to see human proof-of-concept for our insertion technology by Regeneron in their Hemophilia A program. As we look ahead to the rest of the year, we are well positioned for near-term value creation. We have three Phase III programs actively recruiting and one singular focus: getting the work done to enable three launches between 2027 and 2030. We are excited by our progress and by our prospects. So we look forward to sharing data from both of our programs later this year. Lastly, I would like to take this time to welcome Birgit Schultes, our newly appointed Chief Scientific Officer. She is an outstanding scientist with over 20 years of experience in drug development and biotechnology, including the clinical development of cell therapies and complex biologic products. She has experience with our entire suite of gene editing technologies and is leading our more concentrated in vivo and ex vivo research efforts. I'll now hand the call over to our Chief Medical Officer, David Lebwohl, who will provide an update on our clinical programs.

Thanks, John. I'll begin with 2002 in development for HAE. As John noted, we dosed the first patient with 2002 in our HAELO Phase III study last month. As a reminder, the HAELO study is a 60-patient global, randomized, double-blind placebo-controlled study. This is an exciting milestone for Intellia and the HAE community. We see high interest for 2002, which we believe will drive rapid enrollment of our Phase III study and commercial uptake once approved. Based on the promising data we presented thus far, we believe patients could achieve a functional cure. In other words, freedom from HAE attacks and independence from chronically administered prophylactic medications that are commonly used to treat this disease. We plan to present longer-term data from the Phase I/II study later this year, including patients in the Phase II portion who initially received a 25 milligram dose or placebo and were subsequently given the 50 milligram dose of 2002 selected for the Phase III study. With HAELO well underway, we believe 2002 is well positioned to be the first ever one-time treatment for people living with HAE. The therapy is administered with a simple infusion and no need for extended steroids or other preparative drugs. This transformative therapy would also be the first approved using in vivo CRISPR gene editing. Let's move on to nex-z in development for the treatment of ATTR amyloidosis. Starting with ATTR amyloidosis with cardiomyopathy, enrollment in the pivotal Phase III MAGNITUDE study is progressing ahead of our target enrollment projections, and we expect cumulative enrollment to exceed 550 total patients by year-end. In November, we presented data from the Phase I study at the 2024 American Heart Association Scientific Sessions and published the findings in the New England Journal of Medicine. Across all 36 patients, a single dose of nex-z led to rapid, deep and sustained serum TTR reduction, regardless of baseline levels, through the latest follow-up. At month 12, the mean serum TTR reduction was 90% from baseline, and the mean absolute residual serum TTR concentration was 17 micrograms per ml. All patients achieved deep and durable TTR reduction after a one-time infusion. Notably, the TTR reduction occurred rapidly with a native reached at 28 days. When every day matters, achieving TTR reduction as quickly as possible is crucial in this life-threatening illness. With TTR silencers, the reported mean reduction was approximately 80%, which is not reached until six months after starting chronic treatment. Now, we have observed that the very low levels of circulating TTR seen with nex-z are associated with disease stabilization or improvement across several markers of cardiac progression at month 12 compared to baseline. These favorable results were observed even though half of the patients met criteria for Class III heart failure and about 30% had a mutated TTR gene, both characteristics of patients with more rapidly worsening disease. This is a significant insight because when patients are untreated, disease progression as measured by these markers is typically evident within 12 months. In addition to the favorable results across markers of cardiac disease progression, we have also observed a low rate of cardiac hospitalizations in our Phase I study despite the advanced patient population treated with nex-z. This event rate, if reproduced in our pivotal trial, will be associated with a compelling clinical benefit for patients suffering from ATTR cardiomyopathy. Now on to ATTR amyloidosis with polyneuropathy. Patients are actively screening in the Phase III MAGNITUDE-2 study and we are on track to dose the first patient in the coming weeks. At last November’s investor event, we presented data from the Phase I study. Across all 33 patients who received a dose of 0.3 mg/kg or higher, the mean serum TTR reduction was 91% and the mean absolute residual serum TTR concentration was 20 micrograms per ml at month 12. Consistent with the observations of ATTR-CM, the rapid, deep and durable reduction in serum TTR observed in all patients was accompanied by evidence of disease stabilization or improvement across multiple clinical measures of neuropathy. Across NIS, mNIS+7 and mBMI, there were favorable trends of clinical benefit at month 12 compared to baseline levels with further improvements noted in this and mBMI in the part one patients for whom 24 months of follow-up was available. Nex-z has continued to demonstrate a favorable safety and tolerability profile. In recognition of the potential clinical importance of nex-z for the treatment of ATTRv-PN, the FDA granted nex-z Regenerative Medicine Advanced Therapy Designation or RMAT. This will enable closer collaboration with the FDA as we approach a BLA filing in 2028. We look forward to presenting longer-term data from both ATTR-CM and ATTRv-PN patients in the Phase I study later this year. The data will include updated measures of clinical efficacy and safety. Regarding our research platform, we are dedicated to using our toolbox to bring forward breakthrough products, both in vivo and ex vivo. You will hear more about that in the time to come. I will now hand over the call to Ed, our Chief Financial Officer, who will provide an update on our financial results as of the fourth quarter of 2024.

Thank you, David. Good morning, everyone. Intellia continues to maintain a solid balance sheet that allows us to execute on our pipeline and platform. Our cash, cash equivalents and marketable securities were approximately $861.7 million as of December 31, 2024, compared to $1 billion as of December 31, 2023. Our collaboration revenue was $12.9 million during the fourth quarter of 2024, compared to negative $1.9 million during the fourth quarter of 2023. The $14.8 million increase was mainly driven by the Regeneron license and collaboration agreement. R&D expenses were $116.9 million during the fourth quarter of 2024, compared to $109 million during the fourth quarter of 2023. The $7.9 million increase was primarily driven by the advancement of our lead programs. Stock-based compensation included in R&D expenses was $24.4 million for the fourth quarter of 2024. G&A expenses were $32.4 million during the fourth quarter of 2024, compared to $29 million during the prior year quarter. The $3.4 million increase was primarily related to stock-based compensation. Stock-based compensation included in G&A expenses was $15.2 million for the fourth quarter. As we turn our focus to the future, I want to share a few thoughts regarding the restructuring we announced on January 9 and how this changes the complexion of our GAAP operating expenses. In the first quarter of 2025, we expect to incur wind down costs associated with certain programs like NTLA-3001 that have been discontinued or deprioritized. We expect the difficult decisions made to reduce our workforce and focus our pipeline will result in year-over-year declines in GAAP operating expenses of approximately 5% to 10%. The operating leverage and savings created in 2025 are expected to benefit the company over the next couple of years and allow us to make important investments in commercial infrastructure and capabilities while keeping total company expenses below the level of reported results in 2024. While we anticipate greater sales and marketing investments in 2027 to support a successful commercial launch of NTLA-2002 in HAE, the company’s capital needs to support multiple Phase III studies will begin to diminish during that year as some of these programs complete enrollment and supporting costs naturally wind down. We expect to incur approximately $8 million in severance and other employee termination-related costs. Finally, we expect our cash balance to fund our operating plans into the first half of 2027.

Thanks, Ed. In conclusion, Intellia continues to deliver on the promise of gene editing, and we look forward to sharing more clinical progress with you mid-year. With that, we will now open the call for your questions. To do our best to address as many questions as possible, we will only be able to take one question per caller. Operator, you may now open the call for Q&A.

We will now start the question-and-answer session. The first question comes from Mani Foroohar with SVB Securities. Please proceed.

I don’t know about SVB Securities, but thanks for taking the call guys. Can we have – can you help give us a little bit of an update on the tempo of OpEx decline over the course of this year and as you execute on the restructuring? And looking out over the course of the next several years, there has been a lot of concern from investors around OpEx ramp as you have large pivotal studies growing. Can you clarify that a little bit to the extent to which that OpEx ramp is going to happen or the extent to which we just think more in terms of stabilization from clinical trial costs around the pivotal stage? I know this is a little bit of a compound question, but broadly, if you could help people, help us, I suppose, trace out the trajectory of that OpEx over the course of those pivotal trials that would be really helpful.

So Mani from Leerink. Thank you for the question. Obviously, I made some comments about the rate of spend and how the restructuring addresses that, but maybe Ed, you can give some additional details on what you think the trajectory of spend is going to be over the coming years here?

Yes. So I’ll say a few things. Thanks for the question, Mani. As we reported operating results this morning, operating expenses on a GAAP basis were up, I think, 7% year-over-year. That’s pretty consistent with how the company has had momentum in terms of supporting this evolution from a research-based company into a clinical-stage organization. That evolution, as you know, is expected to continue. So we are committed to fully investing in the clinical programs that we have. That’s reflected in the financial guidance that we have provided for 2025. And we are very committed to building the U.S. infrastructure, at least initially, to support the launch of NTLA-2002 in the U.S. In my prepared remarks, I gave commentary to help with 2025 guidance. If I can put a little bit more color on this year in particular, the first quarter will be a little bit noisy. Having announced this on January 9, we have some wind-down costs associated with some of the programs. But you’ll begin to see the effect already in the first quarter and that benefit will continue to accrue throughout the course of 2025. What makes this dynamic and complicated to be overly prescriptive at this point is the reality of what you described as the three Phase III studies that we have ongoing. So those costs are well underway for MAGNITUDE and cardiomyopathy. There are costs now associated with the HAELO study for which we dosed the first patient, and we still expect to dose the first patient in our third Phase III study, MAGNITUDE-2. So you’ll see some increase in costs that are offsetting the benefits that will come with the restructuring. So two will offset the cost of the restructuring will be the investment that we make in the U.S. for the commercial infrastructure that’s required. As you get beyond 2025, though, we kind of hit a steady state. We’re fully enrolled in HAELO at that point by 2026. We’ll be well on our way within the MAGNITUDE-2 study and we’ll be substantially on our way with MAGNITUDE. So we kind of hit steady state in 2026 and for which we’ll get into 2027, costs will begin to naturally sunset and wind down for the HAELO program, then MAGNITUDE-2 and then ultimately MAGNITUDE. So I think it’s important just to take a step back. We have made significant restructuring efforts that allow us to make the investments we need in the new priorities for the company, particularly clinically and commercially oriented. And it’s hard for me to see a scenario in 2025, 2026, or at least through the first part of 2027 where our OpEx is at the level of what we’ve seen this past year in 2024. So I do think peak operating expenses are behind us. The only thing we’ll have to assess closer to the launch will be what incremental investments we need to support NTLA-2002 and HAE.

That’s really helpful. Thanks for taking the question. I know you guys have a lot of those online as well.

Hi, good morning. Thanks for taking my question. For nex-z or 2001, what’s the latest regarding your assumptions on Phase III events accrual rate based on longer-term data that you have? And are you saying more on what would enable the interim analysis for the MAGNITUDE-3 study at this point?

Maybe David, you can address how we’re thinking about the event rates for the MAGNITUDE study and lay out some of our initial thinking for the interim analysis?

Yes. For nex-z?

For MAGNITUDE, yes.

Yes. So this study is, as you know, enrolling at a very good rate. We’re ahead of what our projections were. And the evolution of events, we expect to be similar to the other recent studies, acoramidis and vutrisiran. So now there is a lot of data available on events rates in this disease. The management of disease has not changed significantly from the time of those trials. So that’s what we’re expecting. We haven’t said exactly what that is publicly, but you could see it from the historical data. In terms of the interim analysis, what we have said is what we’ve seen in our trial is from the Phase I results that look quite favorable. They look very good. There is a low event rate in this population suggesting that the patients are benefiting from therapy both in terms of stabilization and even improvement. And this does look different from all the other treatments for TTR that are out there in which the patients as a population continue to get worse. So based on that, we are obviously going to follow-up this data carefully this year. We’ll be seeing the evolution of the events in our MAGNITUDE trial. But based on that, we will be able to in the future give better estimates about the interim. But there is based on what we’re seeing, a good possibility that we could see favorable findings at the interim analysis that would allow us to stop the program earlier. So we will, but there’ll be more details about this from us as time goes on.

Got it. That’s helpful. Thanks for taking my questions.

Great. Thanks so much for taking our question. This is Lisa on for Luca. We saw earlier this week that Alnylam is moving forward with a next-generation TTR silencer and they’re proceeding with a pivotal trial design, which is about 2x the size of their HELIOS-B trial. So we’re just curious if this larger trial size has made you reflect on the MAGNITUDE study and if you are considering making any trial changes such as increasing your patient population size. Any color here would be helpful. Thanks.

Thanks, Lisa. Maybe I can make a couple of comments and David, if you see fit to add, be my guest. We always look at data and we always look at what the competition is doing and think about that very carefully in terms of what it means for the program that we’re carrying out any information that we can gather that helps us think more clearly and accurately about where we’re going is always helpful. We do see important differences, however, and David has touched on how we’re using some of the clinical data that we’ve accumulated already in observations that come from patients who have been treated with our own drug. I think for details in terms of how Alnylam is approaching their work, I would encourage you to ask them. However, I imagine that one of the considerations will be they’re looking to achieve an effect on top of Taf, which was not seen in the earlier study and I’m sure they’re doubling down to try to capture that. We think we’ll be in a really strong position with respect to that category of patients. And also my guess would be that the proportion of patients who are taking Tafamidis will only increase over time and so there will be a far greater proportion of patients taking that drug in their study as that plays out. Those are some top-line comments. I’m sure they have their reasons for some additional details. But with respect to our own work, we’re quite pleased with the design we have. And as David said, as we continue to look at event rates as they occur in our own Phase I patient population that influences how we think about adjusting if at all the trial that we’re doing.

I just may mention one observation about the Alnylam announcement is that you see that they are talking more and more about how important it is to get to lower levels of TTR. And that was actually new slides very close to our slides showing that as in AL amyloidosis, you see that patients who get very low levels have a better result as well as in polyneuropathy, the greater the TTR reduction, the better result. So this is good to see in a sense that they are now agreeing with the hypothesis that we have about lowering of TTR.

Hi, this is Yuri on for Kostas. Congrats on the progress and thanks for taking the question. So we have another question on nexiguran. Can you provide your thoughts on the potential competition from nexiguran and ATTR-CM that has q6M dosing, strong TTR knockdown and can launch around the same time as nex-z? Thank you.

You’re asking about AMVUTTRA, right? Yes. I’m sorry, it was a little unclear. Well, I don’t know if it’ll launch around the same time. We’ll see how that all plays out. Clearly, people are trying to move very, very quickly to get improved therapies to the market. Our basic perspective, I think, was captured by David, which is, this is all about reading TTR levels from the body to the greatest extent possible. And what we’ve seen thus far certainly in the patient population is that we’ve gotten to extremely low levels. We’ve presented not just percentage reduction, but the absolute levels of TTR, which I think is the more meaningful measure just with respect to AMVUTTRA, which is what we expect to be in the market sooner. We’re talking about levels that are about a third with nex-z that compared to what’s been reported for AMVUTTRA. So we’ll see how it plays out with the follow-on compound for Alnylam. But we think that certainly a one-and-done therapy that allows physicians and patients being treated by them to have access to the drug that will have benefits essentially that are in place we suspect for the rest of their lives will be critically important. And I would point out that when it comes to pricing of these drugs, access to insurance, the authorization procedures that are necessary to have year-on-year dosing, we think will be in an advantageous position. So we like where we are. And as you heard from David, the study is progressing well. We expect that we will meet our objectives and look forward to bringing the product to the market.

Thank you. What makes you feel confident to pick 550 patient numbers by year end for the enrollment regarding the ATTR cardiomyopathy trial? Does that mean you will see your trial enrollment in first half 2026 for the total 765 patients?

Gena, thanks for the question. You know us well, we under-promise and over-deliver. And that’s been the guidelines for how we’ve run the company and how we talk about who we are, where we’re going and how we do our work. When I say 550 patients by the end of the year, you can count on that being a very highly likely outcome. Yes, we’ve said that we expect enrollment of the study to be done by 2027. In almost any scenario that we can imagine, even if we were to adjust the trial, once we see the AMVUTTRA data or as we get additional exposure to our own event rates, we are confident that we will fall within that timeframe. But meanwhile, you can count on those 550 patients being enrolled because I see the enrollment rates and we’re not going to give patient-by-patient updates, but it’s rolling robustly and doing very well.

Hi there. Good morning and thank you for taking my question. Maybe just one on sort of the commercial approach here. We’ve seen some gene therapies enter the market for chronic conditions where there’s an established standard of care, and some of those had some issues with reimbursement, leading the company to even discontinue it. Pfizer did with their hemophilia B gene therapy last week. I guess, what can you do now to kind of make sure that the reimbursement environment is favorable and you can drum up patient interest so that specifically in HAE where there is that a sample standard of care, you’ll be commercially viable? Thank you.

Well, it’s an important question. And when we think about, I would start by pointing out that we don’t think gene therapy, certainly the application of AAV to supply missing genetic function is the relevant comparator. Gene editing, which is a really readily straightforward application procedure, is something quite different from the compounds that you mentioned. I’ll just remind you and the other listeners that when we think about dosing patients with our drug, there is a very straightforward treatment regimen that consists of a single dose of dexamethasone the day before therapy. And then on an outpatient basis, and I repeat outpatient basis, patients come in, get another dose of dexamethasone, some antihistamines, a two to four hour infusion, and go home. That is the regimen. Extended steroids, biological product handling, et cetera, just doesn’t apply in this case. So with respect to as you said drumming up interest, it starts with the performance of the drug. And in the case of HAE, remember what we’ve presented thus far, an entirely new category of response for these patients. We’re talking about following a single application, patients having what we have been calling a functional cure, which is the absence of attacks and the absence of the need to take any ongoing therapy. If you ask patients what they want, that is exactly what they’re looking for. So I think a good proxy for how the drug will be received in the marketplace will be the enrollment of the study. And I can report at this time that well, we’ve certainly talked about dosing our first patient. We have patients waiting at multiple clinical trial sites. So we expect this to go very, very well. And I think that’s an indication of patient response. With respect to payers, that work is already underway. And we think we will have a very favorable profile that we’ll be able to present to not just patients themselves, but to the physicians and the payers. And so we look forward to talking more about that as the year goes on.

Hey, guys. This is Matthew on for Alec. Thanks for taking our question. Maybe a quick one from us on the HAE Phase I/II follow-ups. Looking at sort of the incomplete responders, any color on how these patients are doing currently with a longer follow-up period and what you’re expecting or hoping to see in the next update in 2025?

Thanks for the question. I’ll start with a topic sentence or two and then David can fill in some of the details. But I would just point out that the nomenclature used is probably inappropriate. Every single patient has responded, and every single patient is better off than the patient was before they came into the trial. Most of the patients that we reported in that short 16-week observation period for Phase II had a response that we have been terming a functional cure. That is they’ve been able to be in their therapy, and they have no ongoing attacks. We’ve treated patients or offered to patients who are in the placebo arm in the Phase II study or in the 25 milligram dose, the opportunity to be redosed at the Phase III dose of 50 milligrams, and we’ll be in a position to report on those patients and the extended follow-up of the other patients from the Phase II group, both for the duration of those patients who have already achieved a functional cure and those patients who had not yet achieved that during the 16-week observation period. I would point out in our Phase I work, we’ve seen that patients mature in terms of the response over time, and we expect that to be occurring as well for patients in the Phase II side. David, if you want to provide any other color or any other?

Yes. That’s the most important thing. Obviously, we’re going to wait until we give our report about how those patients are doing. But to just reiterate what John has mentioned, what we’ve seen over time is that patients improve. It may be related to the fact that they now know they’re on the drug, but it certainly is what we’ve been seeing and we will talk to you more about that in these patients from the Phase II later this year.

Thanks for taking our questions this morning. Maybe going back to HAE, how should we think through the gating factor as you get ready for the BLA filing? Outside of the clinical package that we’re waiting for from HAELO, what are some of the other important items that you need to align between now and then? Thank you.

Maybe I’ll say a few words and then David you could add just in terms of being in a position to file the BLAs. I mean, we’ve said that our objective is to file a BLA in 2026. I can say next year now, it’s becoming quite close and obviously based on some of the earlier questions, we’re thinking about the market and being prepared for that. But in terms of the product itself and the filing that we’re putting in place, obviously that will consist of the preclinical package, which is done. It has the continued observation of our Phase I and Phase II patient population and then the Phase III data that will come from the phase from the HAELO study, which we’ll be reporting out in the first part of next year as that study completes. It’s important to note that the product itself is in really good shape. We’re using the commercial form of the product in our Phase III trial. So some of those things that can take place where some companies try to bridge to the commercial product, that work is done. And we think we’re going to be in a really good position to move very quickly. I would add that we have RMAT designation for the product and that already puts us in a strong position to deal in an accelerated fashion with the FDA. We’ve been using that designation to our advantage and we expect that that will be very meaningful as the review ensues. Can you add to?

Just to add that we’ve had multiple interactions with the FDA, very favorable interactions, and all the things that John is saying, we think we will be ready for the BLA.

Hey, good morning, and thanks for taking the question. I wanted to follow-up on Ed’s comments around the marketing build-out for 2002 and the associated costs. Could you comment on how big of a sales force you anticipate needing to launch 2002 and what other preparations need to be built out prior to a commercial launch? And if I heard correctly, it sounded like most of the spend would take place in 2027. So I just wanted to confirm you don’t anticipate significant spend here in 2026?

Yes. Thanks, Rick. So we’re not going to describe the size of the sales force. I think we look at the opportunity as a well-defined market. Patients know each other. There are good patient advocacy groups. It’s a well-established market opportunity. We think the footprint to operationalize that is relatively tidy and neat for a company our size. And so we’re very confident in our ability to create that infrastructure and have a very successful launch. The investment in this broader commercial consideration started already in 2024. We’ve brought in senior leadership that has very relevant experience, particularly in HAE. And we have very clear plans in 2025 and 2026 to further extend that leadership team. We’ve had a number of questions today already on market access and pricing considerations. We’ve made that important hire. So we have more senior leadership coming on board in 2025. As we get into 2026 with the BLA filing, we’re sort of that T minus 24 or T minus 12 months in. And so we’re thinking about hiring additional marketing and sales force at that time. So we don’t think it’s a significant investment relative to the other aspects of our business, particularly the clinical expenses. But we’ve got a very clear two-year plan on the expertise we need, the hiring plan to achieve that such that we’re ready for launch in 2027.

Hi. Thank you for taking the question. Also on HAE, you talked about how some patients may be experiencing pseudo attacks that will potentially go away with the longer follow-up, especially if they know they’ve been treated. So it sounds like the data you collect in the long-term observation portion of the Phase III could be pretty important to demonstrating functional cure. I think that would be collected after you submit the original BLA. So I was wondering if you thought about how long you’d want to follow those patients in the long-term observation before submitting a supplemental filing, would it need to be the full 104 weeks or could you do it sooner if it’s clearly apparent that all the attacks have stopped? Thank you.

David, can you outline how we think of long-term follow-up and what’s shared with the FDA and when?

Yes. So it is true we won’t have the 104 weeks at the time of the initial filing. However, by the time we do have the approval, we will be close to having all that data on the patients, including recall many patients crossing over in the Phase I and II experience or receiving the drug in Phase I and II. So we would think about it as a supplemental BLA fairly soon after the initial approval as we think about it right now.

So there'll be lots of data to come over.

This concludes the question-and-answer session and Intellia Therapeutics’ fourth quarter and full-year 2024 financial results conference call. The conference has now concluded. Thank you for attending today’s presentation. You may now disconnect your line.